Amyloid β-peptide (Aβ) containing plaques and neurofibrillary tangles (NFT) are the two major histopathological hallmarks of Alzheimer's disease (AD). According to the amyloid cascade hypothesis, deposition of Aβ is an initial and essential step in the pathogenesis of AD, and formation of NFT has been proposed to be caused by increased Aβ levels. Several previous studies revealed that Aβ plaque formation can be reduced or even prevented by active immunization with Aβ preparations or by administration of Aβ-specific antibodies. To assess the role of fibrillar preparations of Aβ42 in NFT formation, we previously performed intracerebral (i.c.) injections of Aβ42 into brains of NFT-forming P301L tau transgenic mice which caused significant increases in NFT numbers. To determine whether these increases in NFT can be blocked or reduced by active immunization, P301L tau mice were immunized with intraperitoneal injections of preaggregated Aβ42. Aβ42-specific titers were monitored and the mice injected i.c. with Aβ42. We found that i.c. injection of Aβ42 caused significant increases in NFT formation. However, this induction was not affected by active immunization despite high serum anti-Aβ42 titer levels and binding of anti-Aβ42 antibodies to the injected Aβ42 aggregates. We conclude that active immunization is not sufficient to prevent the effect of Aβ42 on tau aggregation in our model system. Further studies are required to determine whether modifications of our protocol could affect the Aβ42-mediated induction of NFT formation.